In an effort to develop a system of somatic cell genetics, we propose to extend our work on transformation with purified chromosomes and to improve the efficiency of transformation mammalian cells. In order to follow the fate of DNA and chromatin complex, we shall use Haemophilus bacterial transforming DNA to test the stability of DNA in eukaryotic cells. Our plan is to stabilize the DNA and no effort will be made to incorporate bacterial genes into the recipient. We also plan to specifically label mammalian cell DNA in vitro and complex it with materials that will protect it from degradation on the recipient cell and use this system to attempt to obtain transformation in mammalian cells. Since we will be using different DNAs, it should be possible to identify systems of restriction and modification in mammalian cells and these can be analyzed both in vitro and in vivo. A major problem in the study of mammalian cell genetics is the availability of selection techniques for isolating rare mutations or variants due to genetic transfer. We propose to explore procedures that we have developed to increase the efficiency of selection in cell culture by 30 to 100 fold or more.